Nucleoside Reverse Transcriptase Inhibitors May Slow the Development of Alzheimer's Disease

Nucleoside reverse transcriptase inhibitors (NTRIs) were developed to treat HIV infection, interfering in the ability of the virus to replicate. Researchers here present epidemiological evidence for this class of drug to slow the onset of Alzheimer's disease. The researchers focus on reduced inflammation as a driving mechanism, but it seems plausible that this outcome occurs because NTRI's interfere in harmful transposable element activities. Transposable elements such as retrotransposons are largely the genetic remnants of ancient viral infections. They make up a sizable fraction of the genome. These sequences are suppressed in youth, but with age and the epigenetic changes characteristic of aging, transposable elements become active, duplicate themselves in the genome to cause mutational damage, create particles that sufficiently resemble viruses to trigger innate immune responses, and cause other harms.

NRTIs, or nucleoside reverse transcriptase inhibitors, are used to prevent the HIV virus from replicating inside the body. Researchers previously determined that the drugs can also prevent the activation of inflammasomes, important agents of our immune system. These proteins have been implicated in the development of Alzheimer's disease, so researchers wanted to see if patients taking the inflammasome-blocking drugs were less likely to develop Alzheimer's.

To do that, they reviewed 24 years of patient data contained in the U.S. Veterans Health Administration Database - made up heavily of men - and 14 years of data in the MarketScan database of commercially insured patients, which offers a broader representation of the population. They looked for patients who were at least 50 years old and were taking medications for either HIV or hepatitis B, another disease treated with NRTIs. They excluded patients with a previous Alzheimer's diagnosis.

In total, the researchers identified more than 270,000 patients who met the study criteria and then analyzed how many went on to develop Alzheimer's. Even after adjusting for factors that might cloud the results, such as whether patients had pre-existing medical conditions, the researchers determined that the reduction in Alzheimer's risk among patients on NRTIs was "significant and substantial." The researchers note that patients taking other types of HIV medications did not show the same reduction in Alzheimer's risk as those on NRTIs. Based on that, they say that NRTIs warrant clinical testing to determine their ability to ward off Alzheimer's.

Link: https://www.eurekalert.org/news-releases/1083000

Comments

Novel (senolytic) vaccine key to reduce Alzheimer's impact:
https://www.drugtargetreview.com/news/111054/novel-vaccine-key-to-reduce-alzheimers-impact/

"Previously, researchers at Juntendo University Graduate School of Medicine in Tokyo, Japan developed a senolytic vaccine targeting senescent cells expressing senescence-associated glycoprotein (SAGP), which demonstrated significant benefits in various age-related diseases, such as atherosclerosis and Type 2 diabetes, in mice. Another study found heightened SAGP expression in glial cells among individuals with Alzheimer's disease. Building on these insights, the scientists examined the efficacy of this vaccine in targeting SAGP-overexpressed cells to treat Alzheimer's disease in mice.

"With Alzheimer's disease affecting 50% to 70% of dementia patients worldwide, our mouse study of this innovative vaccine offers a potential avenue to prevent or modify the disease. The next step will be replicating similar outcomes in humans," said lead study author Chieh-Lun Hsiao, Ph.D., a post-doctoral fellow in the department of cardiovascular biology and medicine at Juntendo University Graduate School of Medicine in Tokyo. "If the vaccine proves successful in humans, it could significantly delay disease progression or even prevent its development.""

Posted by: jimofoz at May 16th, 2025 8:17 AM

I've been experimenting with entecavir and efavirenz for LINE1 suppression.

Transposable elements are also active in cancers.

Structures, functions and adaptations of the human LINE-1 ORF2 protein
https://pmc.ncbi.nlm.nih.gov/articles/PMC10830420/

Posted by: Lee at May 17th, 2025 9:07 AM

@Reason
How do you decide whether to link&cite to EurekAlert, or to the paper itself ( especially when the paper is open-access, like here ) ?

( facebook. com / groups / hbrhs. human. blgcl. rjvntn. hospital. setting. paris )

Posted by: benoît ( paris, france ) at May 19th, 2025 5:34 PM

@Lee
I think I managed to find you online, but I did not find your 'journal' ( dosing, testing ) . 020 / 04 / how-to-plan-and-carry-out-a-simple-self-experiment-a-single-person-trial-of-flagellin-immunization# where-to-publish mentions longecity. org / forum but I don't see the "N=1" publishing section : do you need to be a ( paying ) member to see it ?

( facebook. com / groups / hbrhs. human. blgcl. rjvntn. hospital. setting. paris )

Posted by: benoît ( paris, france ) at May 19th, 2025 7:13 PM
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